Department of Molecular Neuropharmacology

Our research focuses on neuronal mechanisms underlying the activity of the brain’s reward system. We investigate how plasticity in the reward system controls reinforcement learning and how the systems adapts to stress or the effects of drugs of abuse. Additionally, a considerable part of our research involves analysis of gene expression induced by psychoactive substances in the brain structures associated with the reward system. We hope that elucidating molecular signatures of drug action will lead to identification of mechanisms essential for their therapeutic effects.

We conduct behavioral testing on animals with altered neuronal activity by means of genetic modifications or viral transduction. Our laboratory uses a wide variety of behavioral testing methods, including assessment of motor activity, anxiety-like behaviors, memory and all forms of instrumental and pavlovian learning. In the analysis of gene expression we employ several approaches ranging from quantitative PCR to next generation sequencing. Due to the wealth of data generated through gene expression analyses our work has been shifting towards methods data mining and analyses. We had developed and made available to the scientific community several tools that aggregate experimental data and annotations to identify common features among sets of transcript or genes.

Dopamine D1 and D2 Receptors in Chronic Mild Stress: Analysis of Dynamic Receptor Changes in an Animal Model of Depression Using In Situ Hybridization and AutoradiographyDepression is a multifaceted illness that involves altered monoamine
neurotransmission. Many monoamine receptor subtypes (e.g., dopamine D1
and D2) demonstrate altered expression levels in depressed patients and
animal models of depression. Currently, there are an increasing number
of molecular and biochemical studies on the mechanism of stress
resilience. In this chapter, we describe a chronic mild stress (CMS)
procedure along with in situ hybridization and autoradiography protocols
to study changes in brain dopamine receptor expression of rats
subjected to CMS. Chronic mild stress procedure (CMS) is one of few
behavioral animal models of depression, and this model has good
construct, face, and predictive validity. Moreover, approximately 30 %
of rats exposed to stress regimen are stress resilient. There are
numerous biochemical techniques that allow to measure changes in
receptor density and the mRNA expression level. Receptor-specific
radioligand binding measures concentration and visualizes the spatial
distribution of the receptor proteins. In situ hybridization is a
specific probe-based semiquantitative histochemical technique that can
be used to visualize the spatial distribution of RNA sequences in tissue
slices.

Dopamine D1 and D2 Receptors in Chronic Mild Stress: Analysis of Dynamic Receptor Changes in an Animal Model of Depression Using In Situ Hybridization and AutoradiographyDepression is a multifaceted illness that involves altered monoamine
neurotransmission. Many monoamine receptor subtypes (e.g., dopamine D1
and D2) demonstrate altered expression levels in depressed patients and
animal models of depression. Currently, there are an increasing number
of molecular and biochemical studies on the mechanism of stress
resilience. In this chapter, we describe a chronic mild stress (CMS)
procedure along with in situ hybridization and autoradiography protocols
to study changes in brain dopamine receptor expression of rats
subjected to CMS. Chronic mild stress procedure (CMS) is one of few
behavioral animal models of depression, and this model has good
construct, face, and predictive validity. Moreover, approximately 30 %
of rats exposed to stress regimen are stress resilient. There are
numerous biochemical techniques that allow to measure changes in
receptor density and the mRNA expression level. Receptor-specific
radioligand binding measures concentration and visualizes the spatial
distribution of the receptor proteins. In situ hybridization is a
specific probe-based semiquantitative histochemical technique that can
be used to visualize the spatial distribution of RNA sequences in tissue
slices.